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Jeong Sook Kim,
Woong Bin Kim,
Young-Beom Kim, Yeon Lee,
Yoon Sik Kim,
Feng-Yan Shen,
Seung Won Lee,
Dawon Park,
Hee-Joo Choi,
Jinyoung Hur,
Joong Jean Park,
Hee Chul Han,
Christopher S Colwell,
Young-Wuk Cho,
Yang In Kim
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ABSTRACT: In mammals, the increased secretion of arginine-vasopressin (AVP) (antidiuretic hormone) and oxytocin (natriuretic hormone) is a key physiological response to hyperosmotic stress. In this study, we examined whether chronic hyperosmotic stress weakens GABA(A) receptor-mediated synaptic inhibition in rat hypothalamic magnocellular neurosecretory cells (MNCs) secreting these hormones. Gramicidin-perforated recordings of MNCs in acute hypothalamic slices prepared from control rats and ones subjected to the chronic hyperosmotic stress revealed that this challenge not only attenuated the GABAergic inhibition but actually converted it into excitation. The hyperosmotic stress caused a profound depolarizing shift in the reversal potential of GABAergic response (E(GABA)) in MNCs. This E(GABA) shift was associated with increased expression of Na(+)-K(+)-2Cl(-) cotransporter 1 (NKCC1) in MNCs and was blocked by the NKCC inhibitor bumetanide as well as by decreasing NKCC activity through a reduction of extracellular sodium. Blocking central oxytocin receptors during the hyperosmotic stress prevented the switch to GABAergic excitation. Finally, intravenous injection of the GABA(A) receptor antagonist bicuculline lowered the plasma levels of AVP and oxytocin in rats under the chronic hyperosmotic stress. We conclude that the GABAergic responses of MNCs switch between inhibition and excitation in response to physiological needs through the regulation of transmembrane Cl(-) gradients.
Journal of Neuroscience 09/2011; 31(37):13312-22. · 7.11 Impact Factor
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ABSTRACT: Autoimmune hypoglycemia is characterized by hyperinsulinemia, fasting hypoglycemia, and the presence of insulin auto- antibodies without previous exposure to exogenous insulin. We experienced a case of autoimmune hypoglycemia without diabetes mellitus or any evidence of insulinoma. The insulin auto-antibody and insulin receptor auto-antibody were present. We diagnosed the patient as having autoimmune hypoglycemia and treated with glucocorticoid. After treatment, the hypoglycemic symptoms were resolved. However, four months later, the patient was readmitted with transient diabetic ketoacidosis. After recovery, he showed no signs of diabetes mellitus. We believe that insulin auto-antibodies may play a role in autoimmune hypoglycemia and diabetic ketoacidosis, but its role and mechanism are not precisely known. Further studies are needed to define the action mechanisms and the functions of insulin auto-antibodies: here we present case with a relevant literature.
Yonsei Medical Journal 03/2004; 45(1):140-4. · 1.14 Impact Factor
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ABSTRACT: Osteoporosis in men is an important public health problem. Because of the tendency of the numbers of the elderly population to increase, and age-specific incidence of fractures, it is inevitable that the health burden due to fractures will increase. Chronic alcoholism is associated with other risk factors, such as poor nutrition, leanness, liver disease, malabsorption, vitamin D deficiency, hypogonadism, hemosiderosis, parathyroid dysfunction and tobacco use, and these may contribute to the pathogenesis of bone disease related to alcoholism. Chronic alcohol intake may reduce bone density, but can also increase bone density. It is well established that liver disease also induces bone density changes, thus it is difficult to distinguish the role of liver disease from that of alcohol itself in the bone alterations occurring in patients with chronic alcohol consumption. Chronic male alcoholics, not having liver cirrhosis were studied to assess the effect of chronic alcohol consumption on their bone mineral density.
The study subjects comprised of 18 chronic heavy drinkers of more than 40 g of alcohol per day for at least 3 years and 18 age-matched controls who drank less than 20 g of alcohol per day. The serum and urinary parameters of bone and mineral metabolism were determined. The bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry at four axial sites (lumbar spine, femoral neck, Ward's triangle and trochanter).
The alcoholic and control patients drank an average of 97.6 g and 7.2 g of alcohol per day. Osteocalcin, a marker of bone formation, was slightly decreased in alcoholic patients, and deoxypyridinoline, a marker of bone resorption, was slightly increased, but the difference was not statistically significant (p > 0.05). There were no differences between the two groups in the levels of free testosterone, estradiol, 25(OH) vitamin D and parathyroid hormone. The Ward's triangle and trochanter BMDs of the femur were significantly lower in the alcoholics than the controls, and lumbar spine BMD was decreased in proportion to the total alcohol intake in the alcoholics (r = -0.625, p = 0.01).
We suggest that chronic alcohol consumption induces low bone density in the femur Ward's triangle and trochanter. There was also a significant inverse correlation between the lumbar spine BMD and the total amount of alcohol consumed. Large scaled randomized and prospective studies are needed to clarify the pathogenesis of alcohol-induced osteoporosis.
The Korean Journal of Internal Medicine 10/2003; 18(3):174-80.
